The naturally occurring polyamines, putrescine, and spermidine seem to be present universally in living organisms. Although it now appears certain that they are required for optimal rates of growth in microorganisms and animal cells, the precise biological role of these compounds is unknown. Mutants of Escherichia coli have been isolated that require spermidine for optimal growth. The influence of spermidine starvation on the topology of plasmid and chromosomal DNA is being investigated; this will then be related to the known effects of spermidine deficiency on macromolecular synthesis. These in vivo studies with spermidine auxotrophs are being related to the action of polyamines in defined in vitro systems through experiments with a homologous series of spermidine analogs with established biological specificity. The regulation of polyamine biosynthesis is being studied in mitogen-activated lymphocytes, where large increases in the rates of polyamine synthesis and accumulation are observed. In particular, antibodies have been developed to the enzyme S-adenosyl-methionine decarboxylase and these antisera are being used to study the rates of synthesis and degradation of the enzyme in intact cells. Cell-free translation will be used to assay messenger RNA levels and to test the possibility of translational control in this system.